We have identified three new genes expressed in cancer cells: POTE, ankrd26 and NGEP. We have shown NGEP is a cell surface protein expressed on many prostate cancers and promotes the aggregation of LNCAP prostate cancer cells when over-expressed in these cells. In collaboration with Dr Schlom we are working to develop a vaccine for prostate cancer treatment and have identified 2 T cell epitopes as promising vaccine targets. NGEP is a polytopic membrane protein and we have determined its orientation in the plasma membrane. Using this information we are trying to make antibodies to the extra-cellular domains of the protein that can be used to make immunotoxins, immunoconjugates or for other antibody-based therapies of prostate cancer. The other two genes encode intracellular proteins and we are trying to determine their function. Preliminary experiments in which POTE is over-expressed in cells suggest that POTE may promote apoptosis. We have made a strain of mice in which the ankrd 26 gene is partially inactivated and these mice become very obese and also have an increase in organ size. Using the yeast 2 hybrid system we have identified several proteins that appear to associate with ankrd 26 and are using this information to determine the biochemical pathways by which ankrd26 controls obesity. One defect in these mice is that they have very high leptin levels yet continue to eat indicating there is a defect in the brain that makes them leptin unresponsive. We have also prepared antibodies to ankrd26 and are determining which cells in the brain contain ankrd26.